PMID: 8397231Oct 1, 1993

The development of positive inotropic agents for chronic heart failure: how have we gone astray?

Journal of the American College of Cardiology
M Packer


Because cardiac contractility is impaired in chronic heart failure, many pharmacologic agents have been developed to increase the contractile state of the failing heart. These drugs produce impressive hemodynamic effects, but long-term therapy has failed to produce clinical benefits and has increased mortality in treated patients. This experience has led many physicians to suggest that positive inotropic therapy be abandoned as a therapeutic approach for heart failure. However, recent studies suggest that the efficacy and safety of many (if not all) positive inotropic drugs can be greatly enhanced by reducing the dose of these drugs. The importance of dose is dramatically illustrated by the results of trials with vesnarinone, which decreases mortality when used in low doses but increases mortality when administered in doses only twice as large. Although low doses of positive inotropic drugs may be clinically superior to high doses, it is not clear that these low doses exert significant inotropic effects. All positive inotropic drugs exert actions on the circulation in addition to stimulating the heart, and these ancillary properties may be particularly important at low doses of these drugs. Low doses of milrinone and pimobendan...Continue Reading


Oct 19, 2006·JAMA : the Journal of the American Medical Association·Paul J HauptmanThomas E Burroughs
Mar 1, 1995·Clinical Cardiology·M Metra, L Dei Cas
Mar 1, 1996·Cardiovascular Drugs and Therapy·S BertiA Biagini
Jan 1, 1997·Cardiovascular Drugs and Therapy·S Sasayama
Apr 2, 2003·Current Atherosclerosis Reports·Briain D MacNeillRoger J Hajjar
Nov 6, 2004·Current Hypertension Reports·Darrell D Belke, Wolfgang H Dillmann
Oct 1, 1993·Journal of the American College of Cardiology·J S Floras
Jan 19, 1995·The American Journal of Cardiology·G A HaywoodW J McKenna
May 4, 2001·The American Journal of Medicine·G S Francis
Oct 2, 2003·Journal of Molecular and Cellular Cardiology·Jason A Petrofski, Walter J Koch
Oct 1, 1996·Journal of the American College of Cardiology·D J van VeldhuisenK I Lie
Aug 30, 2000·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·C RapezziB Magnani
Jul 10, 1997·The New England Journal of Medicine·J SotoF G Vilchez
Jun 21, 2008·Circulation Research·Leif Erik VingeWalter J Koch
Feb 1, 1995·The Journal of Clinical Investigation·J A Beavo
Aug 31, 2010·Journal of Molecular and Cellular Cardiology·Giuseppe RengoWalter J Koch
Apr 23, 2011·European Journal of Heart Failure·James WinterG André Ng
Jan 15, 2000·Heart & Lung : the Journal of Critical Care·M GheorghiadeR O Bonow
Jun 18, 1998·American Heart Journal·M GheorghiadeR O Bonow
Oct 6, 2005·European Journal of Heart Failure·Corinna B BrunckhorstDaniel Burkhoff
Jul 6, 2015·Heart Failure Clinics·Julie W CreaserGregg C Fonarow
Mar 17, 2015·Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography·Isaac B RheaHarvey Feigenbaum
May 18, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jonathan HullmannWalter J Koch
Jun 1, 1995·Clinical and Experimental Pharmacology & Physiology·A HoeyL Brown
Nov 1, 1995·Clinical and Experimental Pharmacology & Physiology·L Brown
Oct 27, 2001·Acta Physiologica Scandinavica·M J Davidson, Walter J Koch
May 10, 2002·Circulation Journal : Official Journal of the Japanese Circulation Society·Effects of Pimobendan on Chronic Heart Failure Study (EPOCH Study)
Oct 12, 2004·Journal of Cardiovascular Pharmacology·Yoshiyuki SuzukiJun-ichi Imagawa
Sep 17, 2015·Circulation. Heart Failure·Sean P Pinney, Lynne Warner Stevenson
Aug 31, 2013·Circulation Research·Anastasios LymperopoulosWalter J Koch
Jun 1, 1995·Postgraduate Medical Journal·E SmithI R Hastie
Aug 29, 2013·BioMed Research International·Anna KazimierczakGrzegorz Gielerak
Aug 14, 2019·European Journal of Heart Failure·Tariq AhmadJoann Lindenfeld
May 18, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Daniel Burkhoff, Shlomo A Ben-Haim
Feb 12, 2020·Journal of Biochemical and Molecular Toxicology·Jin-Ling FuGuang Shi
Jun 8, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Markus MeyerWolfgang H Dillmann


Nov 19, 1977·Lancet·S M Hull, A Mackintosh
Dec 7, 1976·Virchows Archiv. A, Pathological Anatomy and Histology·P Ebbesen
Dec 21, 1978·The New England Journal of Medicine·J BenottiA A Alousi
Jul 1, 1977·The American Journal of Cardiology·I KhatriE D Freis
Dec 1, 1988·Naunyn-Schmiedeberg's Archives of Pharmacology·S T RapundaloA Schwartz
Dec 1, 1988·Cardiovascular Drugs and Therapy·S H KuboJ N Cohn
Feb 1, 1988·The American Journal of Cardiology·G H GuyattD W Taylor
Aug 1, 1985·Journal of the American College of Cardiology·C A SimontonH Rutman
Jun 20, 1970·British Medical Journal·J L Dall
May 6, 1971·The New England Journal of Medicine·G A BellerW B Hood
Jul 22, 1982·The New England Journal of Medicine·M R BristowE B Stinson
Aug 20, 1984·The American Journal of Medicine·J N Cohn

Related Concepts

Chronic Heart Failure
Peripheral Blood Vessels
Anti-Arrhythmia Agents
Digitalis preparation
Adverse Effects
Inotropic agent
Digitalis Glycosides

Related Feeds

Antiarrhythmic Agents: Mechanisms of Action

Understanding the mechanism of action of antiarrhythmic agents is essential in developing new medications as treatment of cardiac arrhythmias is currently limited by the reduced availability of safe and effective drugs. Discover the latest research on Antiarrhythmic Agents: Mechanism of Action here.


Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.

Anti-Arrhythmic Drug Therapies

Anti-arrhythmic drugs are used to prevent abnormal heart rhythms. These medications are used in conditions including, ventricular tachycardia, ventricular fibrillation and atrial fibrillation. Discover the latest research on anti-arrhythmic drug therapies here.

Cardiology Journals

Discover the latest cardiology research in this collection of the top cardiology journals.